Many sickle cell crises are precipitated by infection, although the mechanism is unclear. We have shown that complement-stimulated granulocytes may slow microvascular flow by embolization, and postulate that such behavior by PMNs might initiate the stagnation of flow that promotes sickling and leads to painful or frankly infarctive crises in a context of complement-activating disease such as infection. Using crosstransfused rats and techniques of intravital microscopy (including fluorescence intravital microscopy with tagged plasma albumin or tagged granulocytes), we proposed to study whether deliberate complement activation wll lead to greater disruption of flow in animals harboring sickle erythrocytes than in animals having their own cells or harboring normal human erythrocytes (preliminary studies suggest this to be so). Further, we will attempt to modify the PMN's response to activated C (e.g. with corticosteroid) in an attempt to block the genesis of such crises. Finally, we hope to apply our intravital microscopic technology to the in-vivo study of insights generated by colleagues in our section who have described abnormal red cell-endothelial cell adhesiveness in sickle disease, and are pursuing means of modifying this phenomenon.